The purpose of the project is to determine if immunologic mechanisms are involved in the pathogenesis of habitual abortion, pre-eclampsia, and intra-uterine growth retardation. Normal preganancy is a paradoxic example of immunologic co-existence of mother and her antigenic fetal-placental unit. This homeostatic balance may go awry in heretofore unexplained complications of pregnancy. Preliminary findings show that women having recurrent spontaneous abortions lack a factor in serum which normally blocks cellular immune reactivity to paternal or cord lymphocytes, as measured by inhibition of macrophage migration (MIF); and that women with pre-eclampsia demonstrate IgM and C3 deposition in vessel lesions in the placental bed by immunofluorescent examination. The objectives of the project are to determine if subjects with the above reproductive problems demonstrate hypersensitivity to paternal, cord, or autologous placental antigens by MIF reactivity, mixed lymphocyte culture, proliferative response, anti-HL-A and direct lymphocyte cytotoxicity, as compared to normal pregnant controls. Different methods of preparation of placental antigens will be compared. The blocking factor for MIF and MLC found in normal pregnancy sera will be further characterized, and compared with immunoglobulins eluted from placentas. Possible blocking antibodies dependent on MLC-related antigens and the LD genetic determinants will be searched for, and complement components and immune complexes measured in circulating blood. Immunofluorescent studies of placental bed vessel lesions will be extended to further characterize the possible immunopathologic process in women and a hamster animal model.